title: Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub-Saharan Africa.
abstract: OBJECTIVE
  To describe immunologic, virologic, and clinical HIV disease progression by HIV-1 subtype among Africans with well documented estimated dates of HIV infection (EDIs).
  
  
  METHODS
  Prospective cohort.
  
  
  METHODS
  Adults and youth with documented HIV-1 infection in the past 12 months were recruited from seroincidence cohorts in East and Southern Africa and followed at 3-6 month intervals. Blood for lymphocyte subset and viral load determination was collected at each visit. Pol was sequenced from the first positive specimen to ascertain subtype. Preantiretroviral therapy disease progression was measured by three time-to-event endpoints: CD4 cell count 350 cells/μl or less, viral load measurement at least 1 × 10 copies/ml, and clinical AIDS.
  
  
  RESULTS
  From 2006 to 2011, 615 participants were enrolled at nine research centers in Kenya, Rwanda, South Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed. Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%). After adjustment for age, sex, and human leukocyte antigen alleles in Cox regression analyses, subtype C-infected participants progressed faster than subtype A to all three endpoints [CD4 hazard ratio 1.60, 95% (confidence interval) CI 1.16, 2.20; viral load hazard ratio 1.59, 95% CI 1.12, 2.25; and AIDS hazard ratio 1.60, 95% CI 1.11, 2.31). Subtype D-infected participants reached high viral load more rapidly (hazard ratio 1.61, 95% CI 1.01, 2.57) and progressed nearly twice as fast to AIDS compared to subtype A (hazard ratio 1.93, 95% CI 1.21, 3.09).
  
  
  CONCLUSIONS
  Subtype-specific differences in HIV disease progression suggest that the local subtype distribution be considered when planning HIV programs and designing and defining clinical endpoints for HIV prevention trials.
authors.affiliation: aInternational AIDS Vaccine Initiative, New York, New York, USA bProject San Francisco, Kigali, Rwanda cMedical Research Council/Uganda Virus Research Unit, Research Unit on AIDS, Entebbe, Uganda dBiostatistics Consultant, Arlington, Virginia, USA eCentre for Geographic Medicine-Coast/Kenya Medical Research Institute, Kilifi, Kenya fUniversity of Oxford, Oxford, UK gZambia-Emory HIV Research Project, Lusaka, Zambia hKenya AIDS Vaccine Initiative, University of Nairobi, Nairobi, Kenya iAurum Institute, Rustenburg jDesmond Tutu HIV Centre, University of Cape Town, Cape Town, Republic of South Africa kEmory University, Atlanta, Georgia, USA lIAVI Human Immunology Laboratory, Imperial College, London, UK.
authors.forename: Pauli N
authors.initials: PN
authors.lastname: Amornkul
authors.forename: Etienne
authors.initials: E
authors.lastname: Karita
authors.forename: Anatoli
authors.initials: A
authors.lastname: Kamali
authors.forename: Wasima N
authors.initials: WN
authors.lastname: Rida
authors.forename: Eduard J
authors.initials: EJ
authors.lastname: Sanders
authors.forename: Shabir
authors.initials: S
authors.lastname: Lakhi
authors.forename: Matt A
authors.initials: MA
authors.lastname: Price
authors.forename: William
authors.initials: W
authors.lastname: Kilembe
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Cormier
authors.forename: Omu
authors.initials: O
authors.lastname: Anzala
authors.forename: Mary H
authors.initials: MH
authors.lastname: Latka
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: Susan A
authors.initials: SA
authors.lastname: Allen
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Fast
mesh_terms: D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019562:Viral Load; D055815:Young Adult